Glycogenesis and Glycogenolysis

Glycogen Metabolism

Glycogen is storage form of glucose in animals as is starts in plants.It is stored mostly in liver and muscles.Glycogen is stored as granules in the cytosol , where most of the enzymes of glycogen synthesis and breakdown are present .

Functions of glycogen:

The primary function of liver glycogen is to maintain the blood glucose level, particularly between meals. Muscle glycogen serves as a fuel reserve for the supply of ATP during muscle concentration.

Fat is the fuel reserve of the body but fat is not preferred,instead, glycogen is chosen for the routine and day to day use of energy for the following reasons

• Glycogen can be rapidly mobilized.Glycogen can generate energy in the absence of oxygen.
• Brain depends on upon continuous glucose supply(which mostly comes from glycogen)

Glycogenesis

The synthesis of glycogen from glucose is called glycogenesis.Glycogenesis takes place in the crystal and requires ATP and VTP beside glucose.

Steps:

Synthesis of UDP-glucose: The enzyme hexokinase and glucokinase convert glucose to glucose-6-phosphate.Phosphoglucomutase catalyzes the conversion of glucose-6-phosphate to glucose-1-phosphate uridine diphosphate glucose (UDPG) is synthesized from glucose-1-phosphate and UTP by UDP-glucose pyrophosphorylase

Requirements of primer to initiate glycogenesis:A small fragment of preexisting glycogen most act as a primer to initiate glycogen synthesis.It is recently found that in the absence of glycogen primer,a specific protein namely glycogen can accept glucose from UDGP.The hydroxyl group of amino acid tyrosine of Glycogenein is the site at which initial glucose unit is attached.The enzyme glycogen initiator synthase transfers the first molecule of glucose to glycogenin.Then glycogenin itself takes up a few glucose residue to form a fragment of primer which serves as an acceptor for the rest of the glucose molecules.

Glycogen synthesis from glycogen synthase :Glycogen synthase is responsible for the synthesis of 1,4 glycosidic linkage.This enzyme transfer’s the glucose from UDP-glucose to the non-reducing end of glycogen to form [alpha]1,4 linkage.

Formation of branches in glycogen: Glycogen synthase can catalyze the synthesis of the linear unbranched molecule with 1,4[alpha] glycosidic linkage.Glycogen, however,is a branched tree-like structure.The formation of branches is brought about by the action of branching enzyme namely glycosyl [alpha]-4,6 transferase.This enzyme transfer a small fragment of 5 to 8 glucose residue from the non-reducing end of glycogen chain to another glucose residue where it is linked by [alpha]-1,6 bond.This leads to a formation of new non reducing ends beside the existing one.Glycogen is further elongated and branched respectively by the enzyme glycogen synthase and glucosyl-4,6-transferase.

The overall reaction of the glycogen synthesis for the addition of each glucose residue is

(Glucose)_n+Glucose+ATP→ (Glucose)(n+1)+2ADP+P_i

Glycogenolysis

The degradation of stored glycogen in liver and muscles constituents glycogenolysis.The pathway for the synthesis and breakdown of glycogen are not reversible and independent set of enzymes present in the cytosol carry out glycogenolysis.Glycogen is degraded by breaking of [alpha]1,4 and [alpha]1,6 glycosidic bonds.

Reactions of glycogenolysis

Action of glycogen phosphorylase (phosphorolysis)

The α-1,4-glycosidic bonds (for the non-reducing ends) are cleaved sequentially by the enzymes glycogen phosphorylase to yield glucose 1-phosphate.This process called Phosphorolysis continues until four glucose residues remain on either side of branching point(α-1,6-glycosidic link).The glycogen so formed is known as limit dextrin which cannot be further degraded by phosphorylase.Glycogen phosphorylase possesses a molecule of pyridoxal phosphate,covalently bound to the enzyme.

Action of debranching enzyme

The branches of glycogen are cleaved by two enzyme activities present on a single polypeptide called debranching enzyme,Hence it is a bifunctional enzyme.Glycosyl 4:4 transferase (oligo α-1,4→1,4 glucan transferase )activity removes a fragment of three or four glucose residues attached to a branch and transfers them to another chain.Here, one α-1,4-bond is cleaved and the same α-1,4 bond is made,but the places are different.Amylo α-1,6-glucosidase breaks the α-1,6 bond at the branch with the single glucose residue and releases the free glucose.The remaining molecule of glycogen is again available for the action of phosphorylase and debranching enzyme to repeat the reactions stated in 1 and 2.

Formation of glucose 6-phosphate and glucose

Through the combined action of glycogen phosphorylase and a debranching enzyme, glucose 1 phosphate and free glucose in the ratio of 8:1 are produced. Glucose 1 phosphate is converted to glucose 6 phosphates by the enzyme phosphoglucomutase. The fate of glucose 6 phosphate depends on the tissues. The liver, kidney, and intestine contain the enzyme glucose 6 phosphatase that cleaves glucose 6phosphate to glucose. The enzyme is absent in muscle and brain, hence free glucose cannot be produced from glucose 6 phosphate in this tissues. There, the liver is the major glycogen storage organ to provide glucose into the circulation to be utilized by various tissues.

Regulation of glycogenesis and glucogenesis

A good coordinate and regulation of glycogen synthesis and its degradation are essential to maintaining the blood glucose levels. glycogenesis and glycogenolysis are respectively controlled by the enzymes glycogen synthase and glycogen phosphorylase. the revelation of these enzymes is accomplished by three machines .

• Allosteric regulation
• Hormonal regulation
• Influence of calcium

Allosteric regulation: There are certain metabolites that allosterically regulates the activities of glycogen synthase glycogen phosphorylase. the controlled is carried out in such a way that glycogen synthesis is increased when substrate availability and energy level is high.

Hormonal regulation: The hormones, through a complex series of reaction, brings about covalent modification, namely phosphorylation and dephosphorylation of enzyme protein which , ultimately control glycogen synthesis or its degradation.

References

Arvind, Keshari K. and Kamal K Adhikari. A Textbook of Biology. Vidyarthi Pustak Bhander.

Michael J.Pleczar JR, Chan E.C.S. and Noel R. Krieg. Microbiology. Tata Mc GrawHill, 1993.

Powar. and Daginawala. General Microbiology.

Rangaswami and Bagyaraj D.J. Agricultural Microbiology.